Permutation entropy of the electroencephalogram: a measure of anaesthetic drug effect

Br J Anaesth. 2008 Dec;101(6):810-21. doi: 10.1093/bja/aen290. Epub 2008 Oct 12.

Abstract

Background: It would be useful to have an open-source electroencephalographic (EEG) index of gamma-amino-butyric acid (GABA)-ergic anaesthetic drug effect that is resistant to eye-blink artifact, responds rapidly to changes in EEG pattern, and can be linked to underlying neurophysiological and neuropharmacological mechanisms that control the conscious state.

Methods: The EEG waveform can be described as a sequence of ordinal patterns. The permutation entropy (PE) describes the relative occurrence of each of these patterns. It is high ( approximately 1.0) when the signal has predominantly high frequencies and low ( approximately 0.4) when the signal consists of only low frequencies. The response of the PE to various computer-generated EEG-like waveforms was assessed. A composite PE index (CPEI) was developed, which was the sum of two simple PEs and included a small measurement-noise threshold (0.5 microV). We also applied the CPEI to two small pilot EEG data sets from patients receiving sevoflurane (n=21) or propofol (n=9) anaesthesia.

Results: With minimal pre-processing or artifact rejection, the CPEI reliably tracked the anaesthetic-related EEG changes, namely loss of high frequencies, spindle-like waves, and delta waves. Using NONMEM, it was possible to construct adequate pharmacokinetic-pharmacodynamic models from the data. The CPEI was comparable with models derived using the bispectral index [BIS R(2)=0.88 (0.08) vs CPEI R(2)=0.91 (0.06) for the propofol data] and M-entropy indices [M-entropy R(2)=0.91 (0.06) vs CPEI R(2)=0.87 (0.09) for the sevoflurane data].

Conclusions: PE of the EEG shows promise as a simple measure of GABAergic anaesthetic drug effect.

MeSH terms

  • Algorithms
  • Anesthetics, General / pharmacology*
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Artifacts
  • Blinking / physiology
  • Consciousness / drug effects
  • Consciousness / physiology
  • Electroencephalography / drug effects*
  • Electroencephalography / methods
  • Entropy
  • Humans
  • Methyl Ethers / pharmacology
  • Monitoring, Intraoperative / methods*
  • Propofol / pharmacology
  • Sevoflurane
  • Signal Processing, Computer-Assisted*

Substances

  • Anesthetics, General
  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Methyl Ethers
  • Sevoflurane
  • Propofol